Joshua Wollen, Abdulwhab Shremo Msdi, Taryn Eubank
Conclusion: Zoliflodacin is a novel, first-in-class spiropyrimidinetrione antibiotic for the treatment of uncomplicated urogenital gonorrhea that is efficacious and provides a novel option for MDR N. gonorrhoeae.
Objective: To review the pharmacology, efficacy, and safety of zoliflodacin for the treatment of uncomplicated urogenital gonorrhea due to Neisseria gonorrhoeae in adults and pediatric patients 12 years of age and older. Data sources and extraction: A literature search was conducted in Scopus, Web of Science, PubMed Central, Gale Academic FileOne, MEDLINE, Journals@Ovid, and Science Direct databases for all articles relevant to zoliflodacin from inception through February 12, 2026. Data synthesis: Preclinical, pharmacokinetic, and clinical trial data have demonstrated that zoliflodacin is effective against multidrug-resistant (MDR) N. gonorrhoeae , with high urogenital cure rates and no current evidence of increasing minimum inhibitory concentrations. Evidence from phase II and III trials supports its single-dose use as an alternative to ceftriaxone; however, the reduced efficacy for pharyngeal and rectal lesions requires additional evaluation. Relevance to patient care and clinical practice in comparison with existing drugs: Zoliflodacin could serve as an oral alternative to ceftriaxone, particularly for patients with a cephalosporin allergy, and be a viable option for resistance-directed therapy. Continued surveillance will be imperative as zoliflodacin use increases. Conclusion: Zoliflodacin is a novel, first-in-class spiropyrimidinetrione antibiotic for the treatment of uncomplicated urogenital gonorrhea that is efficacious and provides a novel option for MDR N. gonorrhoeae.